The lysophosphatidic acid acyltransferases (acylglycerophosphate acyltransferases) family: one reaction, five enzymes, many roles.

Abstract

Lysophosphatidic acid acyltransferases (LPAATs)/acylglycerophosphate acyltransferases (AGPATs) are a homologous group of enzymes that all catalyze the de novo formation of phosphatidic acid from lysophosphatidic acid (LPA) and a fatty acyl-CoA. This review seeks to resolve the apparent redundancy of LPAATs through examination of recent literature. Recent molecular studies suggest that individual LPAAT homologues produce functionally distinct pools of phosphatidic acid, whereas gene ablation studies demonstrate unique roles despite a similar biochemical function. Loss of the individual enzymes not only causes diverse effects on down-stream lipid metabolism, which can vary even for a single enzyme from one tissue to the next, but also results in a wide array of physiological consequences, ranging from cognitive impairment, to lipodystrophy, to embryonic lethality. LPAATs are critical mediators of cell membrane phospholipid synthesis, regulating the production of specific down-stream glycerophospholipid species through generation of distinct pools of phosphatidic acid that feed into dedicated biosynthetic pathways. Loss of any specific LPAAT can lead to alterations in cellular and organellar membrane phospholipid composition that can vary for a single enzyme in different tissues, with unique pathophysiological implications.